MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis.

Ying Chen,Lu Yang,Pei-Feng Xian,Sheng-Xu Wang

doi:10.1155/2016/9279078

Ying Chen, Lu Yang + Show 2 more

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https://doi.org/10.1155/2016/9279078

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Journal: BioMed research international	Publication Date: Jan 1, 2016
Citations: 63	License type: CC BY 4.0

Affiliation: Southern Medical University

Abstract

MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.

Highlights

Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease characterized by inflammation in the joint lining and destruction of cartilage and bone [1]
To compare the nucleoprotein NF-κB and miR-21 levels between Fibroblast-like synoviocytes (FLS) in the RA and normal control groups, we examined the levels of nucleoprotein NF-κB and miR-21 in primary cells using western blotting and Quantitative real-time PCR (Q-PCR) methods, respectively
We found that miR21 and the nucleoprotein NF-κB were upregulated in FLS of RA model rats

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease characterized by inflammation in the joint lining and destruction of cartilage and bone [1]. The contribution of FLS to RA in the synovial intimal lining is especially interesting, and its mechanisms of action are still uncertain. Increasing numbers of reports suggest that aberrant miRNA expression is connected with various diseases and cancers, regulating many biological processes such as cell proliferation [7]. MiR-21, the most commonly upregulated miRNA in various cancers, is upregulated in blood and T cells of patients with RA [10, 11]. Okazaki et al reported that an inhibitor of inhibitory κB proteins (IκB) could suppress the nuclear translocation of NF-κB in FLS and this compound could inhibit the proliferation of rheumatoid FLS and be effective against collagen-induced arthritis in mice [13]. Li et al found that inhibition of miR-21 could significantly

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